WO1999048517A1

WO1999048517A1 - Pharmaceutical compositions for prolonged peptide release and preparation method

Info

Publication number: WO1999048517A1
Application number: PCT/FR1999/000667
Authority: WO
Inventors: Marc Pellet; Frédéric Bismuth
Original assignee: Societe De Conseils De Recherches Et D'applications Scientifiques (S.C.R.A.S.)
Priority date: 1998-03-25
Filing date: 1999-03-22
Publication date: 1999-09-30
Also published as: PT1066049E; NO324621B1; JP2002507578A; ES2200507T3; RU2224538C2; HUP0101545A3; PL343005A1; DK1066049T3; AU756148B2; EP1066049B1; HUP0101545A1; CZ20003432A3; AU2938499A; PL197775B1; DE69908326D1; HU228903B1; FR2776520A1; NO20004741L; FR2776520B1; IL138533A

Abstract

The invention concerns novel solid or semi-solid pharmaceutical compositions comprising a soluble peptide salt capable of jellifying, having a high specific surface area. Said compositions can also comprise an excipient and/or water. Once injected to a patient, the compositions jellify and release the peptide salt for a long time interval not less than 15 days.

Description

PHARMACEUTICAL COMPOSITIONS FOR THE SUSTAINED RELEASE OF PEPTIDES AND THEIR PREPARATION METHOD

The invention relates to novel pharmaceutical compositions intended for the sustained release of peptides and to a process for their preparation.

It had already been described in US Patent 5,595,760 solid and semi-solid pharmaceutical compositions intended for the sustained release of peptides composed of a water-soluble and gelable salt of peptide optionally associated with a suitable monomer excipient. After administration to a patient, these compositions gel and allow sustained release over a period of at least three days.

These compositions provided a considerable advantage over the prior art in terms of their simplicity of manufacture and use.

The Applicant has unexpectedly discovered that it was possible to obtain improved compositions which, while using the same principle, make it possible to obtain a slower release than the conventional compositions, and which in certain cases can reach one, two, three months. or more. In particular, the initial peak (or "burst" in English) is reduced.

In addition, the compositions of the invention are easier to prepare. In particular, the grinding time of the peptide and the force necessary for the kneading can be greatly reduced. The compositions of the invention also have more homogeneous characteristics.

In addition to the advantages mentioned above, some of these compositions have the advantage, for an equal amount of peptide, of requiring a lower injection force and therefore offer better comfort of use. This therefore makes it possible to use syringes having needles with a diameter smaller than that which would be necessary for the equivalent compositions of the prior art.

It is also found that these compositions give very good results during in vivo tests and that the individual experimental differences are reduced, which will make it possible to effectively treat a larger proportion of patients. All these advantages are obtained by giving the peptide a higher specific surface than in the non-matrix compositions (gelling agents) known to those skilled in the art and described in American patent 5,595,760. The gelable compositions according to the invention preferably use peptides whose specific surface has been brought to at least 4 m ² / g, and more preferably to 8 m ² / g or more, this characteristic giving them a slower release profile. and regular. The compositions according to the invention are obtained using a specific lyophilization process comprising a flash-freezing phase of a solution of the peptide, a process which will be described later.

The invention therefore relates first of all to a solid or semi-solid pharmaceutical composition comprising a soluble and gellable salt of peptide optionally associated with a suitable excipient, said pharmaceutical composition being characterized in that the peptide salt has a high specific surface and in that once injected into a patient it forms on contact with bodily matter a gel in this patient, said gel being capable of releasing the peptide over a prolonged period and at least equal to 15 days.

By high specific surface is meant a specific surface greater than that which would be obtained by lyophilization using slow freezing of a solution of a peptide salt. By slow freezing is meant freezing which is not flash freezing as described below or in PCT patent application WO 98/47489.

Preferably, the peptide salt has a specific surface at least equal to 8 m ² / g. and in that once injected into a patient it forms in contact with the bodily matters a gel in this patient, said gel being capable of releasing the peptide over a prolonged period and at least equal to 15 days.

The invention therefore preferably relates to a solid or semi-solid pharmaceutical composition comprising a soluble and gellable salt of peptide optionally associated with a suitable excipient, said pharmaceutical composition being characterized in that the peptide salt has a specific surface at least equal to 4 or 5 m ² / g, and more preferably at 8 m ² / g and in that, once injected into a patient, it forms a gel on this patient in contact with body material, said gel being capable of releasing the peptide onto an extended duration and at least equal to 15 days.

By peptide is meant both peptide and protein. In particular, the peptide salts which can be used for the invention may be chosen from a group composed of the salts of the following substances: triptorelin, lanreotide, octreotide (as described for example in European patent EP 29 579), a compound having an LH-RH activity such as triptorelin, goserelin, leuprorelin, buserelin, an LH-RH antagonist, a GPIIb / IIIa antagonist, a compound having an activity similar to a GPπb / Lïïa antagonist, erythropoietin (EPO) or one of its analogs, the various α interferons, β or γ interferon, somatostatin, a derivative of somatostatin as described in European patent EP 215,171, a somatostatin analog as described in American patent US 5,552,520 (this patent itself includes a list of other patents describing somatostatin analogs which are incorporated by reference to the present application), insulin, a growth hormone (GH), a growth hormone releasing factor (GRF), a growth hormone releasing peptide (GHRP), an epidermal growth factor (EGF) ), a melanocyte-stimulating hormone (MSH), a thyrotropin-releasing hormone (TRH) or one of its derivatives, a thyroid stimulating hormone (TSH), a luteinizing hormone (LH), a follicle stimulating hormone (FSH), a h parathyroid ormone (PTH) or a derivative thereof, a lysozyme hydrochloride, a peptide linked to parathyroid hormone (PTHrp), a fragment of N-terminal peptide (position 1 -> 34) of the human PTH hormone, the vasopressin or one of its derivatives, oxytocin, calcitonin, a calcitonin derivative having an activity similar to that of calcitonin, a peptide linked to the calcitonin gene (CGRP), glucagon, a peptide similar to glucagon ( GLP), gastrin, a gastrin-releasing peptide (GRP), secretin, pancreozymine, cholecystokinin, angiotensin, human placenta lactogen, human chorionic gonadotropin (HCG), enkephalin, a derivative of l enkephalin, colony stimulating factor (CSF), endorphin, kyotorphin, interleukins, e.g. Interleukin 2, tuftsin, thymopoietin, thymosthymline, humoral thymic factor (THF), serum thymic factor (FTS), a derivative of serum thymic factor (FTS), thymosin, thymic factor X, tumor necrosis factor (TNF), motilin, bombesin or one of its derivatives as described in US patent US 5,552,520 (this patent itself includes a list of other patents describing bombesin derivatives which are incorporated by reference into the present application), prolactin, neurotensin, dynorphin, caerulein, substance P, urokinase, asparaginase, bradykinin, kallikrein, nerve growth factor, blood clotting factor, polymixin B, colistin, gramicidin, bacitracin, a peptide stimulating protein synthesis, an endothelin antagonist or one of its derivatives, an intestinal polypeptide vasoactive (VIP), adrenocorticotropic hormone (ACTH) or a fragment thereof, a platelet-derived growth factor (PDGF), a bone morphogenetic protein (BMP), an adeny-activating polypeptide pituitary latecyclase (PACAP), neuropeptide Y (NPY), peptide YY (PYY), a gastric inhibitor polypeptide (GIP). Any water-soluble salt of peptide or protein may also be used by a person skilled in the art if he deems it useful. Preferably, the peptide salt used for the invention will be chosen from a group comprising salts of somatostatin or its analogs, in particular lanreotide acetate or octreotide acetate, triptorelin salts, in particular in particular triptorelin acetate, salts of calcitonin or its analogs, salts of analogs of the hormone LH-RH, salts of the hormones GH, GRF, PTH or of the peptide PTHrp, and analogues of the latter .

The salts of the peptide which can be used for the invention are preferably pharmaceutically acceptable salts of organic acids, such as those of acetic, lactic, malic, ascorbic, succinic, benzoic, methanesulfonic or toluenesulfonic acids, or alternatively pharmaceutically acceptable salts of inorganic acids, such as those of hydrochloric, hydrobromic, hydroiodic, sulfuric or phosphoric acids. They may in particular be acetates of said peptide. The solubility of the peptide salt should, however, be large enough to allow the peptide salt to be frozen with a small amount of solvent.

Preferably, the specific surface of the peptide salt will be at least equal to 4 or 5 m ² / g. More preferably, the peptide salt will have a specific surface at least equal to 10 or 15 m ² / g. Most preferably, the peptide salt will have a specific surface at least equal to 20 m ² / g, or even 30 m ² / g. These specific surfaces can be obtained using the methods described below or in PCT application WO 98/47489.

Said solid or semi-solid composition may comprise from 0 to 30% of an excipient. Excipients which can be used for the invention are pharmaceutically acceptable excipients which facilitate the preparation of the compositions of the invention and / or their administration. The excipients chosen must be water-soluble and biodegradable in contact with body material. They may in particular be polyalcohols such as mannitol and sorbitol, sugars such as glucose and lactose, surfactants, organic solvents or polysaccharides. However, these excipients will not be matrix polymers, such as, for example, polymers of the PLGA type.

To prepare the pharmaceutical compositions of the invention, a process will be used characterized in that it comprises a lyophilization step comprising rapid quenching of a dilute solution of the peptide salt in a medium of temperature below -50 ° C.

By rapid quenching is meant contacting with a medium at low temperature causing instant freezing of the solution of water-soluble substance.

By dilute solution of the peptide salt is meant a solution having a concentration of said peptide salt less than half the saturation concentration, and preferably less than a quarter of said saturation concentration when this is at least equal to 200 g / 1. This process makes it possible to obtain a peptide salt having a high specific surface.

For lyophilization, it is possible, for example, to freeze the solution in a tray bathing in a tank of liquid nitrogen, before carrying out the lyophilization proper.

Preferably, the rapid quenching will be carried out by pouring a dilute solution of the peptide salt onto a metal plate at very low temperature. The temperature of the plate will preferably be less than -70 ° C, and more preferably less than -80 ° C, or even -120 ° C. This quenching makes it possible to obtain a peptide salt having a very high specific surface as described above.

More preferably, in order to obtain a maximum specific surface, the rapid quenching of the solution will be preceded by micronization of the solution of active substance.

If a specific surface greater than 10 m ² / g is necessary, it will be preferable to use the process including a micronization step. Preferably, the specific surface obtained for the active substance after lyophilization will be greater than 15 m ² / g. Even more preferably, this specific surface will be greater than 20 m ² / g, or even 30 m ² / g. The high specific surfaces will be particularly useful because the force necessary for the injection will be lower and the diameter of the needle used for the injection may be less.

For example, to obtain a very high specific surface, one could choose to atomize the solution by spraying it through an atomizer on a plate at very low temperature. The temperature of the plate will be less than -50 ° C, preferably less than -70 ° C, and more preferably still less than -80 ° C, or even -120 ° C. This temperature can be reached for example by soaking the metal plate in a medium at very low temperature such as for example liquid nitrogen. According to a preferred variant of the invention, the metal plate is hollow and the solution is sprayed using an atomizer inside said plate.

Other freezing techniques can be envisaged to obtain a very large specific surface, for example the atomization of the solution of active substance in a bath of non-solvent of the peptide salt previously refrigerated. As non-solvent, a liquefied gas such as liquid nitrogen is preferred. Another possibility is to freeze the peptide salt solution on a refrigerated turntable ("drum-freezing"). As indicated above, this freezing will preferably be preceded by micronization of the peptide salt solution.

The specific surface area of the active substance is a favorable factor for obtaining a release over an extended period. Indeed, particles of a peptide salt of the same size but with different specific surfaces will give completely different results.

To vary the specific surfaces obtained, the freezing conditions of the active substance solution can be varied by varying different parameters such as, for example, the freezing speed or the concentration of the solution.

The lyophilization will be carried out under conventional conditions known to those skilled in the art. After lyophilization, the peptide salt is incorporated, optionally with an excipient, in a solid or semi-solid pharmaceutical composition as described above. This solid or semi-solid composition can be mixed with water as described in US Patent 5,595,760, taking particular account of the fact that water can be present in an amount less than 50% of the amount necessary to dissolve completely the peptide salt, said amount also having to be adapted to give a semi-solid consistency to said composition.

Preferably, when possible, the amount of water added will be less than 30, and more preferably less than 10% of the amount necessary to completely dissolve the peptide salt.

The proportion of peptide in the compositions according to the invention will be determined by the duration of release which it is desired to obtain. However, it will not be able to exceed a maximum value which corresponds to the limit concentration in order to be able to inject the solid or semi-solid composition with a syringe having a needle with a usual diameter. The specific surface area of the peptide may be varied in order to raise said limit concentration if necessary; the higher the specific surface area of the peptide, the lower the injection force, which will make it possible to reduce the diameter of the needle necessary for the injection.

For example, for lanreotide acetate with a high specific surface (for example at least equal to 4 m ² / g) obtained by a lyophilization process comprising a flash freezing step, semi-solid compositions may be used having concentrations comprising 25 or 30% by weight of lanreotide acetate in water (i.e. 20.5 or 24.6% by weight of pure lanreotide). Such compositions can easily be injected with needles with an internal diameter of the order of 1 mm and a length of the order of 32 mm. Preferably, the compositions of the invention based on lanreotide acetate will comprise from 20 to 35%, and more preferably from 25 to 30% by weight of lanreotide acetate.

The mixing of the solid composition and of the water to give semi-solid compositions is preferably carried out in a device made up of two syringes connected to each other. For example, the peptide salt is introduced into one of the syringes and vacuum-conditioned, the water is introduced into the other syringe, and the mixture is homogenized by reciprocating the two pistons. To this end, a person skilled in the art may also usefully consult PCT patent application WO 97/46202.

As indicated above, the semi-solid compositions according to the invention find their use preferably in the pharmaceutical field. The compositions according to the invention can be injected into a patient, for example using the devices described in American patent 5,595,760.

Once injected into a patient, the semi-solid compositions according to the invention form in contact with the bodily matters a gel in this patient, said gel being capable of releasing the peptide over a prolonged period and at least equal to 15 days. Preferably, the release time will be at least equal to 1 month, and more preferably to 2, even 3 months.

Unless otherwise defined, all technical and scientific terms used herein have the same meaning as that commonly understood by an ordinary specialist in the field to which this invention belongs. Likewise, all publications, patent applications, all patents and all other references mentioned herein are incorporated by reference.

The following examples are presented to illustrate the above procedures and should in no way be taken as limiting the scope of the invention.

EXAMPLES;

Methods :

Measuring the specific surface

For all the examples which follow, the specific surface of the peptide salt was determined by the method known as the B.E.T. (absorption of a nitrogen monolayer on the active substance), a method well known to those skilled in the art.

Mixing of peptide and water

For all the examples which follow, the peptide salt and the water are kneaded in a device consisting of two 50 ml syringes connected to each other. The peptide salt is introduced into one of the syringes and vacuum-conditioned, the water is introduced into the other syringe, and the mixture is homogenized by reciprocating the two pistons.

Example 1:

Lanreotide acetate with a specific surface 0.61 m ² / g is dissolved in water at a concentration of 30 g / 1 and is frozen by pouring the aqueous solution obtained into a hollow metal tray cooled to 1 outside with liquid nitrogen. The peptide salt is thus frozen. Lyophilization is then carried out and the lanreotide acetate with a specific surface 5.41 m ² / g is recovered.

3 g of lanreotide acetate thus obtained are mixed with 6.927 ml of water to give a semi-solid paste. The mixture is then kneaded as indicated above to give 10.927 g of a homogeneous and compact semi-solid composition. This composition can be directly used for an injection to the subject to be treated.

Example 2:

9.0 g of lanreotide acetate with a specific surface 1.73 m ² / g are dissolved in 300 ml of water. This solution is then sprayed using an atomizer into a hollow metal tray, the bottom of which dips in liquid nitrogen. The peptide salt is thus frozen. Lyophilization is then carried out and 8.7 g of lanreotide acetate with a specific surface 28.2 m ² / g are recovered.

3 g of lanreotide acetate thus obtained are mixed with 7.183 ml of water to give a semi-solid paste. The mixture is then kneaded as indicated above to give 10.183 g of a homogeneous and compact semi-solid composition. This composition can be directly used for an injection to the subject to be treated. Examples 3 and 4:

The same protocol is used for these two examples

5 g of lanreotide acetate are dissolved in sterile water to give the chosen concentration to the solution. This solution is atomized using a 500 ml sprayer, the jet of which is adjusted so as to obtain the finest droplets possible. The droplets obtained are projected onto a tray, the bottom of which dips in liquid nitrogen. Two temperature probes are previously introduced into the tray in order to monitor the evolution of the product temperature.

Once the product has been frozen, the tray is introduced into the freeze dryer, the plate of which is at approximately -54 ° C.

The temperature of the products and of the plate is allowed to equilibrate for 1 hour. Then we go to the sublimation phase (the temperature of the plate is then fixed at 20 ° C and the pressure in the tank at 100 μbar). This phase lasts about 30 hours. The average final product temperature is around 13 ° C. The following secondary drying (pressure in the tank brought to 50 μbar) lasts for approximately 24 hours. The average final product temperature is 20 ° C.

The characteristics of the reagents used and of the products obtained are summarized in the table below:

Characteristics Example 3 Example 4

Mass of lanreotide acetate used (g) 5.00 5.00

Concentration of the solution (g / 1) 30 10

Mass of lanreotide acetate recovered 4.54 4.10

Specific surface obtained (m ² / g) 36 43

Like the lanreotide acetate of examples 1 and 2, the lanreotide acetate of examples 3 and 4 can be incorporated into semi-solid pharmaceutical compositions by simple mixing with a suitable quantity of water. Study of the properties of compositions according to the invention

Three tests were carried out. The first relates to the force necessary for the injection of a dose of composition obtained according to Example 2, the second on the in vitro release profile of the same composition and the third on the release profile in dogs of the compositions Examples 1 and 2 compared to that obtained for an analogous composition but with a peptide of low specific surface.

Reference

In order to serve as a reference for measuring the release force and the in vitro test, a composition produced according to the following protocol was chosen: Lanreotide acetate is dissolved in water to give a solution of concentration 30 g / 1, which is poured into a hollow tray previously immersed in liquid nitrogen. The lanreotide acetate thus frozen is then lyophilized and incorporated into a solid composition as described in Example 2 above, 6.817 ml of water being added to 3 g of lanreotide acetate to give 9.817 g of semi-composition solid.

Measurement of the force required for injection

Using a dynamometer, the force to be applied to the plunger of the syringe is measured in order to make it progress relative to the displacement of the plunger (quantity of semi-solid composition injected: approximately 280 mg; just like Example 2, the reference contains approximately 0.25 mg of lanreotide acetate per mg of semi-solid composition). By expressing the displacement of the piston in mm as a function of the force applied in N, a three-phase profile is obtained, from which 8 remarkable values are drawn, used to calculate an average value for the force necessary for injection. The value used for each test is the average of 5 measurements made on the same composition.

In vitro release profile

In order to obtain significant results, each composition tested is divided into 6 samples, and the value chosen is the average obtained over the 6 tests. In each case, the semi-solid composition to be tested is placed in a cylindrical dialysis tube equipped with a semi-permeable synthetic membrane. Both ends of the tube are closed. This tube is placed in 20 ml of 0.9% aqueous NaCl solution, the temperature being fixed at 37 ° C. The medium is stirred (magnetic stirrer). Half an hour, 1 h, 2 h, 3 h, 4 h, 24 h, 48 h and 72 h after the start of the test, samples of the NaCl solution are taken and the lanreotide content is determined by UN assay (wavelength: 280 nm).

At the end of the test (after 96 hours for the reference), the residual part of the peptide contained in the dialysis tube is assayed in order to express the results in proportion to the peptide released relative to the total initial quantity.

Results

The results obtained are reproduced in Table I below:

Measured parameters Reference Example 2

Amount of lanreotide in 1 mg 0.252 0.250 gel (in mg)

Specific surface of the acetate of 3.64 28.6 lanreotide incorporated (m ² / g)

Force required for injection (Ν) 41.0 27.3

Dissolved proportion after 0.5 h 1.5 1.0

Proportion dissolved after 1 h 2.7 2.1

Proportion dissolved after 2 h 5.1 4.0

Proportion dissolved after 3 h 7.2 6.1

Proportion dissolved after 4 hrs 9.5 8.0

Proportion dissolved after 24 h 39.3 29.9

Proportion dissolved after 48 h 62.6 38.8

Proportion dissolved after 72 h 77.5 44.7

Proportion dissolved after 96 h 88.4 50.3

Table I Additional measurements were carried out for Example 2 and show dissolved proportions of 57.7% after 144 h, 66.8% after 216 h and 77.7% after 334 h.

It is therefore found that the composition of Example 2, which differs from the reference composition by its specific surface area almost 10 times higher, releases the peptide significantly slower than the reference composition. Furthermore, the composition of Example 2 requires a lower injection force than the reference composition.

In vivo release profile in dogs

The reference composition for this test comprises 30% by weight of lanreotide acetate with a specific surface 0.8 m ² / g (obtained by a lyophilization process using slow freezing), the rest of the composition consisting of the water. The concentration of pure lanreotide of the reference composition and of the composition of Example 2 is therefore 246 mg per gram of composition.

The tests are carried out on two batches of 6 Beagles dogs, each of the dogs receiving an intramuscular injection of 60 mg of reference composition or of composition of Example 2.

Results

The plasma concentrations measured for Examples 1 and 2 (expressed in ng / ml) are reported respectively in Table II below:

Average

Time

Ref. Ex. 2

0 0,000 0,000 0,000

0.083 h 4.909 4.365 3.642

0.25 h 20.930 11.348 14.591

0.5 h 32.215 22.711 17.637 l h 43.215 26.863 24.847

2 h 45.208 32.831 29.262

4 h 44.129 30.112 29.696

8:58.362 30.218 26.713

12:48 p.m. 04,041 20,831 18,235 1 day 29,462 20,771 16,977

2 days 13,677 7,731 13,105

3 days 9,974 8,000 12,248

4 days 6.683 6.716 6.520

8 days 3,583 2,564 3,179

11 days 3,225 2,305 2,513

15 days 1,786 2,280 2,075

18 days 1.305 2.553 1.481

22 days 1,329 2,317 1,097

25 days 1,182 1,582 1,605

29 days 1,024 0.983 0.951

32 days 0.685 0.696 0.924

36 days 0.362 0.486 0.714

39 days 0.194 0.521 0.792

43 days 0.217 0.443 0.715

46 days 0.189 0.332 0.768

50 days 0.153 0.337 0.511

53 days 0.148 0.297 0.513

57 days 0.150 0.228 0.466

60 days 0.131 0.254 0.411

65 days 0.094 0.191 0.281

72 days 0.093 0.120 0.312

79 days 0.044 0.147 0.157

86 days 0.063 0.068 0.200

93 days 0.050 0.072 0.167

100 days 0.046 0.052 0.137

107 days 0.000 0.064 0.107

114 days 0.000 0.057 0.062

122 days 0.000 0.034 0.067

128 days 0.000 0.030 0.048

135 days 0,000 - 0,000

Table II

These in vivo tests confirm that the initial peak (or "burst" in English) is considerably reduced for the compositions of Example 1 and of Example 2 compared to an analogous composition comprising a peptide with a lower specific surface. In addition, the release becomes too low after 60 days for the reference composition while it is sufficient to ensure a plasma level greater than 0.1 ng / ml for at least 79 days for the composition of Example 1 and at least 107 days for the composition of Example 2.

Claims

1. Solid or semi-solid pharmaceutical composition comprising a water-soluble and gellable salt of peptide optionally associated with a suitable excipient, said pharmaceutical composition being characterized in that the peptide salt has a high specific surface and in that when injected into a patient it forms on contact with bodily matter a gel in this patient, said gel being capable of releasing the peptide over a prolonged period and at least equal to 15 days.

. Pharmaceutical composition according to claim 1, characterized in that the gel obtained from the patient is capable of releasing the peptide over a period at least equal to 1 month.

3. Pharmaceutical composition according to claim 1 or 2, characterized in that the gel obtained from the patient is capable of releasing the peptide over a period at least equal to 2 months, and preferably at least equal to 3 months.

4. Pharmaceutical composition according to one of claims 1 to 3, characterized in that the peptide salt has a specific surface at least equal to 4 mAlg, and preferably at least equal to 8 m ^ / g.

5. Pharmaceutical composition according to claim 4, characterized in that the peptide salt has a specific surface at least equal to 10 m - ^ / g, and preferably at least equal to 15 m *** Vg.

6. Pharmaceutical composition according to one of claims 5, characterized in that the peptide salt has a specific surface at least equal to 20 m *** Vg.

7. Pharmaceutical composition according to one of claims 6, characterized in that the peptide salt has a specific surface at least equal to 30 m ^ / g.

8. Pharmaceutical composition according to one of claims 1 to 7, characterized in that an excipient is present in a proportion less than or equal to 30%.

9. Pharmaceutical composition according to claim 8, characterized in that the excipient is chosen from a group of compounds comprising polyalcohols such as mannitol and sorbitol, sugars such as glucose and lactose, surfactants, organic solvents and polysaccharides.

10. Pharmaceutical composition according to one of the preceding claims, characterized in that it also comprises water in an amount less than 50% of the amount necessary to completely dissolve the peptide salt and adapted to give a semi consistency -solid to said composition.

11. Pharmaceutical composition according to one of the preceding claims, characterized in that the peptide salt is chosen from the salts of the following substances: triptorelin, lanreotide, octreotide, a compound having an LH-RH activity such as triptorelin, goserelin, leuprorelin, buserelin, an LH-RH antagonist, a GPIIb / IIIa antagonist, a compound having activity similar to a GPIIb / IIIa antagonist, erythropoietin (EPO) or one of its analogs , the different α interferons, interferon β or γ, somatostatin, a somatostatin derivative, a somatostatin analog, insulin, a growth hormone (GH), a growth hormone releasing factor (GRF) ), a growth hormone releasing peptide (GHRP), an epidermal growth factor (EGF), a melanocyte-stimulating hormone (MSH), a thyrotropin-releasing hormone (TRH) or one of its derivatives, a hormone stimulating the thyro lide (TSH), a luteinizing hormone (LH), a follicle stimulating hormone (FSH), a parathyroid hormone (PTH) or a derivative thereof, lysozyme hydrochloride, a peptide related to parathyroid hormone (PTHrp), a fragment of N-terminal peptide (position 1 -> 34) of the human PTH hormone, vasopressin or one of its derivatives, oxytocin, calcitonin, a calcitonin derivative having an activity similar to that of calcitonin , a peptide linked to the calcitonin gene (CGRP), glucagon, a glucagon-like peptide (GLP), gastrin, a gastrin-releasing peptide (GRP), secretin, pancreozymine, cholecystokinin, angiotensin, human placenta lactogen, human chorionic gonadotropin (HCG), enkephalin, an enkephalin derivative, colony stimulating factor (CSF), endorphin, kyotorphin, interleukins, e.g. Interleukin 2 , tuftsin, thymopoietin, thymosth ymline, humoral thymic factor (THF), serum thymic factor (FTS), a derivative of serum thymic factor (FTS), thymosin, thymic factor X, tumor necrosis factor (TNF), motilin, bombesin or one of its derivatives, prolactin, neurotensin, dynorphin, caerulein, substance P, urokinase, asparaginase, bradykinin, kallikrein, nerve growth factor, blood clotting factor, polymixin B, colistin, gramicidin, bacitracin, a peptide stimulating protein synthesis, an endothelin antagonist or a derivative thereof, a vasoactive intestinal polypeptide (VIP), adrenocorticotropic hormone (ACTH) or a fragment thereof , a growth factor platelet derivative (PDGF), a bone morphogenetic protein (BMP), a polypeptide activating pituitary adenylatecyclase (PACAP), neuropeptide Y (NPY), peptide YY (PYY), a gastric inhibitor polypeptide (GIP).

12. Pharmaceutical composition according to claim 11, characterized in that the peptide is chosen from a group comprising salts of somatostatin or its analogs, in particular lanreotide acetate or octreotide acetate, salts of triptorelin, in particular triptorelin acetate, salts of calcitonin or its analogs, salts of hormone LH-RH analogs, salts of the hormones GH, GRF, PTH or the peptide PTHrp, and the like of these.

13. Pharmaceutical composition according to claim 11 or 12, characterized in that the peptide is triptorelin acetate.

14. Pharmaceutical composition according to claim 11 or 12, characterized in that the peptide is lanreotide acetate or octreotide acetate.